PXD033447 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning |
Description | Precise vascular patterning is critical for normal growth and development. The ERG transcription factor drives Delta like ligand 4 (DLL4)/Notch signalling and is thought to act as pivotal regulators of endothelial cell (EC) dynamics and developmental angiogenesis. However, molecular regulation of ERG activity remains obscure. Using a series of EC specific Focal Adhesion Kinase (FAK)-knockout (KO) and point-mutant FAK-knockin mice, we show that loss of ECFAK, its kinase activity or phosphorylation at FAK-Y397, but not FAK-Y861, reduces ERG and DLL4 expression levels together with concomitant aberrations in vascular patterning. Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins identified that endothelial nuclear-FAK interacts with the de-ubiquitinase USP9x and the ubiquitin ligase TRIM25 enzymes. Further in silico analysis corroborates that ERG interacts with USP9x and TRIM25. Moreover, ERG levels are reduced in FAKKO ECs via a ubiquitin-mediated post-translational modification programme involving USP9x and TRIM25. Re-expression of ERG in vivo and in vitro rescues the aberrant vessel sprouting defects observed in the absence of ECFAK. Our findings identify ECFAK as a regulator of retinal vascular patterning by controlling ERG protein degradation via TRIM25/USP9x. |
HostingRepository | PRIDE |
AnnounceDate | 2022-07-05 |
AnnouncementXML | Submission_2022-07-05_03:21:17.211.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alex von kriegsheim |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-04-25 04:09:16 | ID requested | |
⏵ 1 | 2022-07-05 03:21:18 | announced | |
Publication List
D'Amico G, Fernandez I, G, รณ, mez-Escudero J, Kim H, Maniati E, Azman MS, Mardakheh FK, Serrels B, Serrels A, Parsons M, Squire A, Birdsey GM, Randi AM, Bolado-Carrancio A, Gangeswaran R, Reynolds LE, Bodrug N, Wang Y, Wang J, Meier P, Hodivala-Dilke KM, ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning. Development, 149(13):(2022) [pubmed] |
Keyword List
submitter keyword: RIME, HUVEC, FAK |
Contact List
Alex von Kriegsheim |
contact affiliation | University of Edinburgh |
contact email | avonkri@ed.ac.uk |
lab head | |
Alex von kriegsheim |
contact affiliation | University of Edinburgh |
contact email | alex.vonkriegsheim@ucd.ie |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD033447
- Label: PRIDE project
- Name: ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning